Key messages
- Calcium channel blockers, a medicine given to people with a kidney transplant to lower their blood pressure, probably prevent death and the loss of the transplanted kidney but may make little or no difference to kidney function compared with placebo (dummy medicine) or standard care.
- The blood pressure-lowering medicines, angiotensin-converting-enzyme inhibitors and angiotensin receptor blockers, may make little or no difference to death, the loss of the transplanted kidney or kidney function.
- We are not sure whether any other blood pressure medicines are beneficial or cause unwanted effects.
Why treat blood pressure in people who have received a kidney transplant?
High blood pressure (hypertension) often occurs in people who have received a kidney transplant. This affects the blood vessels and may lead to heart attack, stroke, or interruption of the blood supply to other organs, including the kidney transplant itself, which may lead to the loss of the transplanted kidney. Blood pressure medicines (also known as antihypertensives) are used to treat high blood pressure and aim to lower blood pressure to healthy levels. The main blood pressure-lowering medicines given to people who have received a kidney transplant are calcium channel blockers, angiotensin-converting-enzyme inhibitors and angiotensin receptor blockers.
What did we want to find out?
We wanted to find out if blood pressure-lowering medicines given to people with a kidney transplant prevent death and the loss of the transplanted kidney and improve kidney function, compared with placebo (dummy medicine).
What did we do?
We searched for all trials that assessed the benefits and harms of blood pressure-lowering medicines for treating people who have received a kidney transplant. We compared and summarised the trials' results and rated our confidence in the information based on factors such as trial methods and size.
What did we find?
We found 97 studies involving 8706 people with a kidney transplant. The biggest study involved 820 people, and the smallest study involved 9 people. The studies were conducted around the world; most were done in Europe (49). Most studies lasted for around 12 months, with a range from 2 weeks to 5 years. Pharmaceutical companies funded 26 of the studies.
- Calcium channel blockers probably prevent death and the loss of the transplanted kidney. However, they may make little to no difference in preventing the rejection of the transplanted kidney or increasing kidney function.
- Angiotensin-converting-enzyme inhibitors and angiotensin receptor blockers may make little to no difference in preventing death, rejection, or loss of the transplanted kidney or in increasing kidney function.
- We are uncertain about the effects of other blood pressure-lowering medicines.
What are the limitations of the evidence?
We are moderately confident that calcium channel blockers prevent death due to any cause and the loss of the transplanted kidney; however, we are less confident they may prevent rejection of the kidney or improve kidney function because of concerns about how some of the studies were conducted.
We are less confident in the results of other blood pressure-lowering medicines because of the small number of studies included and concerns about how some of the studies were conducted.
How up to date is the evidence?
The evidence is current to July 2024.
For kidney transplant recipients, the use of CCB therapy to reduce BP probably reduces death and graft loss compared to placebo or standard care alone, while ARB may reduce graft loss. The effects of ACEi and ARB compared to placebo or standard care on other patient-centred outcomes were uncertain. The effects of dual therapy, alpha-blockers, and mineralocorticoid receptor antagonists compared to placebo or standard care alone and the comparative effects of different treatments were uncertain.
The comparative effects of specific blood pressure (BP) lowering treatments on patient-important outcomes following kidney transplantation are uncertain. Our 2009 Cochrane review found that calcium channel blockers (CCBs) improved graft function and prevented graft loss, while the evidence for other BP-lowering treatments was limited. This is an update of the 2009 Cochrane review.
To compare the benefits and harms of different classes and combinations of antihypertensive drugs in kidney transplant recipients.
We contacted the Information Specialist and searched the Cochrane Kidney and Transplant Register of Studies up to 3 July 2024 using search terms relevant to this review. Studies in the Register were identified through searches of CENTRAL, MEDLINE, EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov.
Randomised controlled trials (RCTs) and quasi-RCTs evaluating any BP-lowering agent in recipients of a functioning kidney transplant for at least two weeks were eligible.
Two authors independently assessed the risks of bias and extracted data. Treatment estimates were summarised using the random-effects model and expressed as relative risk (RR) or mean difference (MD) with 95% confidence intervals (CI). Evidence certainty was assessed using Grades of Recommendation, Assessment, Development and Evaluation (GRADE) processes. The primary outcomes included all-cause death, graft loss, and kidney function.
Ninety-seven studies (8706 participants) were included. One study evaluated treatment in children. The overall risk of bias was unclear to high across all domains.
Compared to placebo or standard care alone, CCBs probably reduce all-cause death (23 studies, 3327 participants: RR 0.83, 95% CI 0.72 to 0.95; I2 = 0%; moderate certainty evidence) and graft loss (24 studies, 3577 participants: RR 0.84, 95% CI 0.75 to 0.95; I2 = 0%; moderate certainty evidence). CCBs may make little or no difference to estimated glomerular filtration rate (eGFR) (11 studies, 2250 participants: MD 1.89 mL/min/1.73 m2, 95% CI -0.70 to 4.48; I2 = 48%; low certainty evidence) and acute rejection (13 studies, 906 participants: RR 10.8, 95% CI 0.85 to 1.35; I2 = 0%; moderate certainty evidence). CCBs may reduce systolic BP (SBP) (3 studies, 329 participants: MD -5.83 mm Hg, 95% CI -10.24 to -1.42; I2 = 13%; low certainty evidence) and diastolic BP (DBP) (3 studies, 329 participants: MD -3.98 mm Hg, 95% CI -5.98 to -1.99; I2 = 0%; low certainty evidence). CCBs have uncertain effects on proteinuria.
Compared to placebo or standard care alone, angiotensin-converting-enzyme inhibitors (ACEi) may make little or no difference to all-cause death (7 studies, 702 participants: RR 1.13, 95% CI 0.58 to 2.21; I2 = 0%; low certainty evidence), graft loss (6 studies, 718 participants: RR 0.75, 95% CI 0.49 to 1.13; I2 = 0%; low certainty evidence), eGFR (4 studies, 509 participants: MD -2.46 mL/min/1.73 m2, 95% CI -7.66 to 2.73; I2 = 64%; low certainty evidence) and acute rejection (4 studies, 388 participants: RR 1.75, 95% CI 0.76 to 4.04; I2 = 0%; low certainty evidence). ACEi may reduce proteinuria (5 studies, 441 participants: MD -0.33 g/24 hours, 95% CI -0.64 to -0.01; I2 = 67%; low certainty evidence) but had uncertain effects on SBP and DBP.
Compared to placebo or standard care alone, angiotensin receptor blockers (ARB) may make little or no difference to all-cause death (6 studies, 1041 participants: RR 0.69, 95% CI 0.36 to 1.31; I2 = 0%; low certainty evidence), eGRF (5 studies, 300 participants: MD -1.91 mL/min/1.73 m2, 95% CI -6.20 to 2.38; I2 = 57%; low certainty evidence), and acute rejection (4 studies, 323 participants: RR 1.00, 95% CI 0.44 to 2.29; I2 = 0%; low certainty evidence). ARBs may reduce graft loss (6 studies, 892 participants: RR 0.35, 95% CI 0.15 to 0.84; I2 = 0%; low certainty evidence), SBP (10 studies, 1239 participants: MD -3.73 mm Hg, 95% CI -7.02 to -0.44; I2 = 63%; moderate certainty evidence) and DBP (9 studies, 1086 participants: MD -2.75 mm Hg, 95% CI -4.32 to -1.18; I2 = 47%; moderate certainty evidence), but has uncertain effects on proteinuria.
The effects of CCBs, ACEi or ARB compared to placebo or standard care alone on cardiovascular outcomes (including fatal or nonfatal myocardial infarction, fatal or nonfatal stroke) or other adverse events were uncertain.
The comparative effects of ACEi plus ARB dual therapy, alpha-blockers, and mineralocorticoid receptor antagonists compared to placebo or standard care alone were rarely evaluated.
Head-to-head comparisons of ACEi, ARB or thiazide versus CCB, ACEi versus ARB, CCB or ACEi versus alpha- or beta-blockers, or ACEi plus CCB dual therapy versus ACEi or CCB monotherapy were scarce. No studies reported outcome data for cancer or life participation.